Table 1.
Summary of retrospective studies on IORT use in recurrent head and neck cancer.
| Reference | Na | Primary location (most common) | Median tumor sizee | IORT location | IORT modality | Dose range | Median dose | Adjuvant therapy at rec. | Hx of RT | Duration to reirradiation | Median F/U | LC | Survival | Toxicity |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Scala et al. (9) | n = 76 (87 sites) | Oral cavity (29%), SGT (18%), OP (16%) | Median field size: 5 = 6 cm | Neck (46%); face (13%) | HDR IORT | 12–17.5 Gyb | 12 Gy | 24% EBRT (45 Gy) 41% (chemo) | EBRT: (59.8–63.9 Gy) | 2 years | 11 months | 2 year IFLC: 62% | MS: 33 months (in field control) and 17 months (no control) | Flap revision: 4%, carotid hemorrhage: 1%, vagal neuropathy: 1% |
| Teckie et al. (10) | n = 57 (59 sites) | OP, hypopharynx, SGT | ≤2 cm: 42% 2.1–4 cm: 32% >4 cm: 25% |
Neck (71%); parotid (12%) | HDR IORT | 12–20 Gy | 15 Gy | 21% EBRT: (50 Gy) 27% (chemo) 11% (both) | EBRT: median dose: 66 Gy | Median: 15 months | 16 months | 3-year IFPFS: 57% | 3 year OS: 50% (in field control) vs. 32% (no control) | Fibrosis: 29%, trismus: 24%, cellulitis: 10%, CN injury: 26%, dysphagia: 39%, fistula: 15% |
| Zeidan et al. (11) | n = 46 (out of 96 total) | Parotid gland | ≤2 cm: 47% 2.1–4 cm: 39% >4 cm: 14% |
Parotid (100%) | IOERT (Mobetron) | 15 Gy or 20 Gy | 15–20 Gy | 57% EBRT (45 Gy), 19% chemo | EBRT: median dose: 60 Gy | 8.7 months | 5.6 years | 5 year RFS: 48.1% (recurrent) | 3 year OS: 59%, 5 year OS: 48% (recurrent)c | Comp.: 27% vascular: 7%, trismus: 6%, ORN: 4%, fistulas: 4%, flap necrosis: 2%, wound dehiscence: 2%, neuropathy 1% |
| Zeidan et al. (12) | n = 198 (out of 231 total) | UAD tract | 4.3 cm | Neck (100%) | IOERT | 10–25 Gy | 15–20 Gy | 22% EBRT (45 Gy), 43% chemo | EBRT: dose not reported | NR | 1.03 years | 3 year RFS: 55%, 5 year RFS: 49% (for all) | 3 year OS: 34%, 5 year OS: 26% (for all) | Vascular: 11.3%, fistula: 9.8%, wound dehiscence: 9.8%, neuropathy: 3%ORN: 4% |
| Perry et al. (6) | n = 34 | Salivary gland (21%) and OP (21%) | ≤2 cm: 53% 2.1–4 cm: 26% >4 cm: 21% |
Salivary gland (21%) and OP (21%) | HDR-IORT | 10–20 Gy | 15 Gy | 15% EBRT: (50 Gy) 21% chemo | EBRT: median dose: 63 Gy | median: 16 months | 23 months | 2 year LC = 56% | 2 year OS = 55%, MS = 24 months | Fibrosis: 38, trismus: 23%, cellulitis: 14%, fistula or wound: 9%, ORN 3%, trigeminal neuralgia: 3%, 2nd tumor: 3% |
| Chen et al. (2) | n = 37 (out of 99) | SGT (100%) | ≤2 cm: 28% 2.1–4 cm: 41% >4 cm: 30% |
SGT (100%) parotid most common (34%) | IOERT | 12–18 Gy | 15 Gy | 15% EBRT (54 Gy) 9% chemo | EBRT: median dose 60 Gy | 3.1 years | 3.7 years | 5 year LC: 82% (with IORT) and 60% (without IORT) | 3 year OS: 54%, 5 year OS: 34% (all). MS: 12 mo. (neck rec) vs. 20 months (primary site rec) | Superficial wound infection: 5%, trismus: 3%, Facial neuropathy: 3% |
| Chen et al. (4) | n = 137 d | OP, oral cavity, paranasal sinus, parotid. | ≤2 cm: 45% 2.1–4 cm: 33% >4 cm: 22% |
Local (64%); neck (28%); both (8%) | IOERT | NR | 15 Gy | 26% EBRT (54 Gy) 72% chemo | EBRT median dose: 64 Gy | 13 months | 18 months | 3 year in field control: 62% 3 year LRC 51% |
3 year OS: 36% (3-year OS: 44% primary rec compared with 19% neck rec) | Superficial wound infection: 3%, fistula: 1.5%, wound dehiscence: 0.7%, trismus: 0.7%, neuropathy: 0.7% |
| Pinheiro et al. (13) | n = 44 (34 SCC and 10 non-SCCd) | OP, oral cavity | NR | Skull base (56%) and neck (44%) | IOERT | 12.5–22.5 Gy | NR | NR | NR | NR | 6.3 years | 2 year LF: 54% (SCC) and 48% (non-SCC) | 2 year OS: 50% (non-SCC) and 32% (SCC) | Soft tissue: 11.3%, fistula: 6.8%, neuropathy: 11.3%, fatal hemorrhage: 2.2%, wound: 4.5% |
| Schleicher et al. (14) | n = 84 (113 sites) | Hypopharynx, larynx and OP | Median field size: 34 cm2 | Jugular chain (80%) | IOERT | 10–20 Gy | 20 Gy | 9.5%: chemo | EBRT: median dose: 56 Gy | median: 38.3 weeks | NR | LC: 24% R2, 41.7% R1, 50% R0 | MS = 6.8 months | Wound healing: 9%, 4%, salivary fistula: 3.5%, necrosis: 2% |
| Nag et al. (15) | n = 38 | Larynx and oral cavity | NR | Primary H&N site (29%), neck only (37%) | IOERT | 15 Gy: close or microscopically + margins, 20 for gross | 15 or 20 Gy | 0% EBRT | EBRT: median dose 65.1 Gy | NR | 30 months | 2 year LC = 13%, 2 year LRC: 4% | 2 year OS: 21%, 3 year OS: 8% | Comp.: 16%, orocutaneous fistula: 5%, fatal fistula, wound or tracheal dehiscence and carotid occlusion: 2.6% each |
| Martinez-Monge et al. (16) | n = 23 (31 total) | NR | NR | NR | IOERT | 10–15 Gy | NR | NR | EBRT: median dose 50 Gy | NR | NR | 2 year LRC: 26%: recurrent | 2 year OS: 31% (recurrent) | Comp.: 10% |
| Ling et al. (17) | n = 25 (out of 30 total) | NR | NR | NR | IOERT | 15 Gy | 15 Gy | NR | NR | NR | 30 months | 3 year LRC: 60% (for all) | 3 year OS: 70% (for all) | Comp.: 16% |
| Freeman et al. (18) | n = 52 (out of 75 total) | NR | >3 cm | Neck (100%) | IOERT | 10–25 Gy | 20 Gy | 33% EBRT (Dose NR) | EBRT: dose NR | NR | 2 years | 2 year LC: 68%: all patients | 2 year OS: 45% (all patients) | Comp.: 25% including carotid blowout, sepsis, ORN, PE, flap necrosis, MI and hypocalcemia |
| Toita et al. (19) | n = 17 (22 sites out of 24 total) | Oral cavity (46%) | NR | Neck (86%); primary (14%) | IOERT | 10–30 Gy | 20 Gy | 67% EBRT (41.2 Gy) | EBRT: 26–70 Gy range | NR | 19 months | 2 year LC: 54% allf GR: 0% MR: 55%, CM: 82% | 2 year OS: 45%; 0% GR, 33% MR, 70% CM (all) | Comp: 22%, carotid blowout: 3 patients, osteoradionecrosis (all more than or = 20 Gy): 4 sites |
| Freeman et al. (3) | n = 64 (out of 104 total) | Mucosa of UAD tract (71%), SGT (23%) | NR | Neck (35%), skull base (19%), parotid (17%) | IOERT | 15–20 Gy | 20 Gy: neck, 15 Gy: skull base, oral cavity and SG | NR | NR | NR | 2 years | 2 year LC: 40% (all) | NR | ORN: 6%, fistulas: 6%, carotid blowout: 3%, MI and PE: 3% |
IORT, intraoperative radiation therapy; IOERT, intraoperative electron radiation therapy; HDR IORT, high-dose brachytherapy; F/U, follow-up; LC, local control; IFLC, in-field local control; IFPFS, in-field progression-free survival; RFS, recurrence-free survival; OS, overall survival; SGT, salivary gland tumor; OP, oropharynx; SCC, squamous cell carcinoma; Comp., complications; ORN, osteoradionecrosis; EBRT, external beam radiation therapy; RT, radiation therapy; LRC, locoregional control.
aN: patients with recurrent tumors who received IORT.
b12 Gy: negative margins, 15–17.5 Gy for microscopically positive margins.
c1% LR in the IORT field, 20% regional, 13% distant in all.
dIt included primary and recurrent tumors.
eMedian field size, when available, is given when median tumor size is not reported.
fLC: 78% primary and 43% for neck.